Reply: The Role of Inflammation and Gender Differences in the Pathogenesis of Cardiac Arrhythmias.
Reply: The Role of Inflammation and Gender Differences in the Pathogenesis of Cardiac Arrhythmias.
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DOI：
10.1016/j.jacbts.2023.03.018
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发表时间：
2023-06
影响因子：
9.7
通讯作者：
Capecchi, Pier Leopoldo
中科院分区：
文献类型：
--
作者：
Lazzerini, Pietro Enea;Abbate, Antonio;Acampa, Maurizio;Boutjdir, Mohamed;Capecchi, Pier Leopoldo
众所周知，性别相关因素显著影响Brugada综合征（BrS），其临床疾病表达在男性中比女性高8至10倍。[2]同样众所周知的是，发热是BrS患者室性心律失常（VA）的一个重要促发因素，在男性中更为常见（仅20%的病例发生在女性，且几乎全部发生在非生殖期）。[3]尽管人们普遍认为发热是通过Nav 1的温度依赖性生物物理变化降低钠电流INa而起作用的。5通道，1，4，雌激素对该电流的影响似乎是最小的。2因此，可以推测涉及额外的炎症介导的机制，可能有助于解释性别差异。事实上，细胞因子是发热的基本介质，几乎所有发热诱导的BrS和相关VA的病例都发生在活动性炎症性疾病的背景下。此外，即使在没有发热的情况下，也有更多的BrS病例被炎症过程所掩盖，5全身和/或心肌炎症是新认识到的BrS的重要致炎底物。6，7在这种情况下，越来越多的炎症细胞因子的电生理效应可能会显着促进BrS的临床表达，至少部分是通过它们对心脏连接蛋白-43表达的快速下调作用。1，4事实上，已经证明，在BrS右心室流出道心外膜连接蛋白-43表达减少，并与危及生命的VA相关。8然而，成年女性的心肌细胞显示连接蛋白-43水平比男性高50%，9由于雌二醇介导的作用也降低了VA的脆弱性，10可能导致女性的易感性降低。
It is well recognized that sex-related factors significantly impact Brugada syndrome (BrS), whose clinical disease expression is 8 to 10 times higher in men than in women. 2 Equally well known is that fever is an important precipitating factor for ventricular arrhythmias (VAs) in BrS, more commonly in males (only w20% of cases occur in females and almost exclusively in nonreproductive periods). 3 Although it is generally accepted that fever acts by reducing the sodium current INa via temperaturedependent biophysical changes of the Nav1. 5 channel, 1, 4 the impact of estrogens on this current seems to be minimal. 2 Therefore, it can be speculated that additional inflammation-mediated mechanisms are involved, possibly helping to explain sex differences. Indeed, cytokines are the fundamental mediators of fever, and practically all cases of fever-induced BrS and related VAs occurred in the setting of active inflammatory diseases. Moreover, cases of BrS unmasked by inflammatory processes even in the absence of fever are ever more reported, 5 and systemic and/or myocardial inflammation is newly recognized as an important arrhythmogenic substrate in BrS. 6, 7 In this scenario, it is likely that the increasingly recognized electrophysiological effects of inflammatory cytokines may significantly contribute to the clinical expression of BrS, at least in part via their rapid down-regulating effects on cardiac connexin-43 expression. 1, 4 Indeed, it has been demonstrated that in the BrS right ventricular outflow-tract epicardium connexin-43 expression is reduced and correlated with lifethreatening VAs. 8 Nevertheless, cardiomyocytes from adult females show w50% higher connexin-43 levels than in males, 9 due to estradiol-mediated effects also reducing VA vulnerability, 10 possibly contributing to lower susceptibility for women.
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影响因子：
3
作者：
Stauffer BL;Sobus RD;Sucharov CC
通讯作者：
Sucharov CC
影响因子：
0.9
作者：
Adedeji OM;Falk Z;Tracy CM;Batarseh A
通讯作者：
Batarseh A
影响因子：
24
作者：
Pieroni, Maurizio;Notarstefano, Pasquale;Bolognese, Leonardo
通讯作者：
Bolognese, Leonardo
影响因子：
9.7
作者：
Lazzerini, Pietro Enea;Abbate, Antonio;Boutjdir, Mohamed;Capecchi, Pier Leopoldo
通讯作者：
Capecchi, Pier Leopoldo
Brugada综合征的纤维化，连接蛋白43和传导异常。
影响因子：
24
作者：
Nademanee K;Raju H;de Noronha SV;Papadakis M;Robinson L;Rothery S;Makita N;Kowase S;Boonmee N;Vitayakritsirikul V;Ratanarapee S;Sharma S;van der Wal AC;Christiansen M;Tan HL;Wilde AA;Nogami A;Sheppard MN;Veerakul G;Behr ER
通讯作者：
Behr ER